Bordetella bronchiseptica is capable of infecting the respiratory tracts of many animals particularly mammals. B. bronchiseptica is the cause of atrophic rhinitis and pneumonia in swine. Harris and Switzer, Am. J. Vet. Res., 30, 1161-1166 (1969). A related disease in swine is commonly referred to as "turbinate atrophy" because following the primary B. bronchiseptica infection, the nasel turbinate bones frequently undergo serious deterioration. See Switzer and Farrington U.S. Pat. No. 4,016,253 (1977).
In dogs, B. bronchiseptica has been characterized as the primary etiological agent in infectious canine tracheobronchitis more commonly known as kennel cough. Wright et al, Vet. Rec., Nov. 3, 1973, 486-487; Appel et al, Cornell Research Laboratory for Disease of Dogs, Laboratory Report, Series 2, No. 6 (May, 1976). The latter publication states that kennel cough is a highly contagious respiratory disease of dogs which, although not life-threatening, should be prevented. The disease causes suffering to the dogs and is unpleasant for dog owners. It is commonly transmitted when dogs are placed in kennels for boarding.
Other mammalian species are also afflicted with B. bronchiseptica infections. These include laboratory animals such as guinea pigs, rabbits, and rats, as well as animals raised for meat or fur, such as rabbits and chinchilla. See Nakagawa et al, Jap. J. Vet. Sci., 33(2), 53-60 (1971); Oldenburg et al, Monatshefte fur Veterinarmedizin, 27(19), 738-743 (1972); Burek et al, Lab. An. Sci., 22(6), 844-849 (1972); Ioakimidis et al, Kteniatrika Nea Thessaloniki, 2, 31-33 (1970). B. bronchiseptica may also cause pneumonia in monkeys and other zoo animals. Graves, Lab. An. Car., 20(2), 246-250 (1970). Cats are carriers of B. bronchiseptica and may spread the disease to other animals. Fisk et al, Lab. An. Sci., 23(1) 33-35 (1973).
In the United States, the first successful swine vaccine for preventing turbinate atrophy is manufactured and sold by Burns-Biotec Laboratories, Inc. in accordance with Switzer and Farrington U.S. Pat. No. 4,016,253. This patent describes a parenteral vaccine for intramuscular injection prepared from killed whole cells of strain D-1 (ATCC No. 31124).
In 1973 Daniel O. Farrington and William P. Switzer published positive results of experiments using strain 55 intranasal vaccines for swine. Proceedings of the George A. Young Conference on Advances in Swine Repopulation and the 13th Annual Nebraska SPF Conference, Lincoln, Neb., July 23-24, 1973, pp. 44-52. These and related experiments were more completely reported in the Ph.D. thesis of Daniel O. Farrington, entitled "Evaluation of Nasal Culturing Procedures and Immunization as Applied to the Control of Bordetella bronchiseptica Rhinitis in Swine." Iowa State University, Ames, Iowa, Dr. William P. Switzer, Major Professor. This thesis is on deposit at the Iowa State University Library, Ames, Iowa under call No. 1974-F 249. This thesis also contains a description of the taxonomic characteristics of strain 55. As described in these Switzer-Farrington publications, a concentrated aqueous suspension of strain 55 cells was prepared by culturing strain 55 in tryptose phosphate broth (TPB), and syringe administering 0.5 ml. of the cell suspension into each nostril of the pig, the cultures used containing approximately 1.times.10.sup.7 viable cells per milliliter.
The vaccine developed by Dr. Switzer and Dr. Farrington, as described above, is the subject of U.S. patent application Ser. No. 967,477, filed Dec. 7, 1978, and is administered as an intra-respiratory vaccine. The immunization action is dependent on implant colonization of the respiratory mucosa. Successful implantation relates to the number of viable cells administered, and to the ability of the cells to implant and colonize before they are removed from their respiratory tract. The mucous membranes of the respiratory tract tend to be resistant to the implantation of the cells. On initial administration of the intra-respiratory vaccine containing the viable cells, the ciliated epithelia of the upper respiratory tract respond by trying to clear the cells from the nasal passages. There is also a tendency to clear foreign material from the mouth, throat and tracheae. However, for effective use, a live-cell respiratory vaccine must possess the capability to remain on the respiratory mucosa long enough for the cells to become implanted, form colonies, and thereby create the desired immunizing effect.
Since the cells of strain 55 B. bronchiseptica are highly attenuated, being not only avirulent but self-clearing from the respiratory mucosa, the problem of obtaining effective implant colonization presents particular difficulties. For commercial use, it is desirable for economic reasons and for ease of administration to avoid the use of excessive size doses. Moreover, the intra-respiratory administration may be carried out by relatively untrained people, such as swine raisers, dog owners, etc. Yet, immunization must be effectively obtained with each vaccination, and a hit-or-miss immunization is completely unacceptable for general use of the vaccine.